Approaches to improving in vitro engineered cardiac tissue culture using multimodal stimulation and matrix mechanobiology
Bretherton, Ross C.
- As the leading cause of death in the world, cardiovascular disease is responsible for nearly a third of all mortality. Limited regenerative potential of adult mammalian myocardial muscle and chronic fibrosis lead to maladaptive remodeling of the left ventricle in response to changing mechanical loads, ultimately leading to heart failure. To enhance regeneration and attenuate fibrosis, tissue ... read moreengineering approaches aim to produce mature myocardial muscle in vitro, either for direct implant into patients or to model the complex mechanisms of cardiovascular disease. This thesis approaches cardiovascular tissue engineering from all sides. First, a bioreactor system for the combined electrical and mechanical stimulation of engineered cardiac tissue constructs is redesigned to accommodate long-term and contamination-sensitive disease modelling and stem cell differentiation experiments. Adaptation of a silk-ECM hybrid hydrogel for use in the bioreactor system is attempted, albeit unsuccessfully. The second half of the thesis focuses on signal processing to improve monitoring of cardiac function, both for in vivo experiments using pressure-volume loops, and for bioreactor culture of cardiac tissue using eosin fluorescence. In the near future, we predict these methods of stimulation and analysis will converge, resulting in systems which are able to both stimulate and monitor engineered tissue constructs in real time.read less